Kappa opioid receptor antagonists and products and methods related thereto

Inventors

Roberts, Edward • Guerrero, Miguel A. • Urbano, Mariangela • Rosen, Hugh • Jones, Robert M. • Laxamana, Candace Mae • Zhao, Xianrui • Turtle, Eric Douglas

Assignees

Scripps Research Institute • Neumora Therapeutics Inc

Abstract

Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof: wherein X, Y, R1, R2, R4, R5, R6, R7, R8 and R11 are as defined herein.

Core Innovation

The invention provides pharmaceutical compositions comprising a compound having Formula (I), or pharmaceutically acceptable hydrate, solvate, isotope or salt forms thereof, together with at least one pharmaceutically acceptable carrier, diluent or excipient. The disclosed content includes KOR (OPRK1) antagonists and related substituted heterocyclic compounds, with variable substituents and structural options defined by formula ranges and parameters such as X, Y, and R-group substituents.

The compositions are described with preference for oral administration and multiple oral dosage forms, including tablet, capsule, troche, lozenge, syrup, and emulsion, with additional narrowing to tablet or capsule dosage forms. The document also describes synthetic examples, intermediates, characterization language, stereochemical analogs, representative structures, and pharmacology sections.

Methods of use are described in connection with KOR antagonism and OPRK1 antagonism for treating neuropsychiatric and behavioral conditions. The described conditions include addictive disorders, CNS disorders, anxiety disorders, depressive disorders, mood disorders, schizophrenia and schizoaffective disorder, obesity and eating disorders, migraine, postnatal depression, neurodegenerative disease-associated mood and behavior disorders, anesthesia and/or sedation, epilepsy, status epilepticus, seizure, and serum prolactin reduction.

Claims Coverage

The provided claim content includes one independent claim directed to a pharmaceutical composition, with six inventive features overall when dependent refinements are included. The independent claim covers a Formula (I) KOR antagonist compound, or an allowed derivative form, together with a pharmaceutically acceptable carrier, diluent, or excipient, and dependent claims further specify oral dosage forms and dosing-frequency constraints.

The claim coverage centers on the Formula (I) KOR antagonist compound, including hydrate, solvate, isotope, and salt forms, formulated with a pharmaceutically acceptable carrier. The claims further narrow the composition to oral administration, specified oral dosage forms, and once-daily or two- or three-times-daily tablet or capsule administration.

Stated Advantages

Documented Applications